《生命科学》 2024, 36(6): 771-776

肝再生磷酸酶2的促癌机制及其抑制剂的研究进展

李茹薇¹ , 陶浩强² , 肖奕菲¹ , 王佳银¹ , 于　洁^2,*

¹杭州医学院存济口腔医学院，杭州 310013 ²杭州医学院检验医学院、 生物工程学院，浙江省神经精神疾病药物研究重点实验室，杭州 310013

摘　要：

肝再生磷酸酶2(phosphatase of regenerating liver 2, PRL2) 属于肝再生磷酸酶家族，在人体各个组织器官中广泛表达。PRL2 异常高表达与肿瘤的发生发展和临床预后密切相关，是多种癌症的潜在治疗靶点。研究表明PRL2 通过两种机制发挥促癌作用：一是依赖假磷酸酶活性，主要与镁离子转运体CNNM3 结合；二是凭借磷酸酶活性，使底物分子PTEN 等去磷酸化。因此，阻断PRL2 与CNNM3 结合或抑制PRL2 磷酸酶活性有望成为新的抗癌策略。现综述了PRL2 与不同癌症的联系、其促癌分子机制和抑制剂的最新研究进展。

通讯作者：于　洁 , Email:jyu@hmc.edu.cn

The oncogenic mechanism of phosphatase of regenerating liver 2 and the research progress of its inhibitors

LI Ru-Wei¹ , TAO Hao-Qiang² , XIAO Yi-Fei¹ , WANG Jia-Yin¹ , YU Jie^2,*

¹Savaid Stomatology School of Hangzhou Medical College, Hangzhou 310013, China ²School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Zhejiang Provincial Key Laboratory of Neuropsychiatric Drug Research, Hangzhou 310013, China

Abstract:

The phosphatase of regenerating liver 2 (PRL2), a member of the phosphatases of regenerating liver, exhibits widespread expression throughout various tissues and organs in the human body. Elevated expression of PRL2 is closely associated with the initiation, progression, and clinical outcomes of tumors, rendering it a prospective therapeutic target across various malignancies. Studies indicate that PRL2 functions in cancer progression through two mechanisms: firstly, it leverages pseudophosphatase activity, which mainly interacts with the magnesium ion transporter CNNM3; the second is to utilize phosphatase activity to dephosphorylate substrate molecules such as PTEN. Consequently, strategies aimed at disrupting the interaction between PRL2 and CNNM3 or inhibting the phosphatase activity of PRL2 represent novel avenues for anticancer intervention. This review comprehensively outlines the associations between PRL2 with diverse cancers, elucidating the molecular mechanisms underlying its oncogenic properties and the latest advancements of its inhibitors.

Communication Author：YU Jie , Email:jyu@hmc.edu.cn